ICIs

Immune checkpoint inhibitors (ICIs) are a class of cancer immunotherapy drugs that block inhibitory pathways on T cells, thereby enhancing anti-tumor immune responses. The most established targets are CTLA-4 and the PD-1/PD-L1 axis, with additional targets such as LAG-3 and TIGIT under investigation. By blocking these checkpoints, ICIs aim to sustain T-cell activation and allow the immune system to recognize and attack tumor cells.

Common ICIs include antibodies against CTLA-4 (for example, ipilimumab) and against PD-1 (nivolumab, pembrolizumab, cemiplimab) or PD-L1 (atezolizumab, durvalumab, avelumab). ICI therapy can be given as monotherapy or in combination, most notably a combination of a CTLA-4 inhibitor with a PD-1 inhibitor, which can increase response rates but also the risk of immune-related adverse events.

Indications for ICIs span a range of cancers, including malignant melanoma, non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, and certain colorectal, gastric, and hepatocellular carcinomas, among others. Tumor biology influences response; biomarkers such as PD-L1 expression, tumor mutational burden, and microsatellite instability/mismatch repair deficiency help guide some treatment decisions, though they are not perfect predictors.

Clinical responses to ICIs vary. Some patients experience rapid tumor shrinkage, others achieve durable disease control, and a subset may respond after initial progression. Durable remissions can occur even after discontinuation. Immune-related adverse events (irAEs) can affect the skin, gastrointestinal tract, endocrine system, liver, lungs, and other organs, requiring monitoring, dose modification, or immunosuppressive treatment in severe cases.

Overall, ICIs have transformed outcomes for several cancers, with ongoing research to expand indications, refine patient selection, and optimize combinations and management of irAEs.